Vitamin C is dead

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lymphocyte

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LOVIT. Over 800 patients. Multicentre RCT. Seems well done. Vitamin C demonstrates clear harm. Good bye Vitamin C.

I've worked at tertiary centres where this was being used. Makes me feel a little sick.

I have to be honest and say I was a little bit excited after CITRIS-ALI. But I'm becoming ever more cynical and jaded and better understanding of my older colleagues who've seen it all before when it comes to new trials.

Also: Van den Berghe with the Leuven trials and tight glycemic control. Rivers and EGDT. Marick and his cocktail. You either die a hero or live long enough to become the villain.

Also: low tidal volumes, antibiotics, arguing about source control, and being meticulous about not doing anything stupid. Is that all we have to offer as a speciality? I'm only half joking. It's painful to see yet another negative trial.

Conclusion:
In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo.

Methods:
In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28.

Results:
A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P=0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event.


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Also: low tidal volumes, antibiotics, arguing about source control, and being meticulous about not doing anything stupid. Is that all we have to offer as a speciality? I'm only half joking. It's painful to see either yet another negative trial.

I mean... there are plenty of studies that show that implementation of lung protective ventilation strategies are much lower than they should be and being meticulous about not doing anything stupid is actually a lot of work that goes unappreciated. I mean, there's an entire part of SCCM's PADIS bundle that is, "You should try to extubate everyone daily" and another that's "you should control pain" because... apparently people aren't doing those things.
 
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Was Vitamin C ever alive?

Time clouds the picture, but I think I remember hearing about Marik’s (single center, very small) trial, then the immediate explosion in lay media about a “sepsis cure”, followed by an almost-as-immediate “waaaaaaait a minute….is this too good to be true?”. Then study after study after study after study showed no mortality benefit from the Vit C or the cocktail.
 
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Was Vitamin C ever alive?

Time clouds the picture, but I think I remember hearing about Marik’s (single center, very small) trial, then the immediate explosion in lay media about a “sepsis cure”, followed by an almost-as-immediate “waaaaaaait a minute….is this too good to be true?”. Then study after study after study after study showed no mortality benefit from the Vit C or the cocktail.

Alive enough to launch study after study after study. Which other intensive care interventions generated that much research interest in the past five years?
 
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Being meticulous about not doing anything stupid is harder than it sounds imo 😄

I’ve often argued that our focus on being experts at “supportive care” is our downfall. Supportive care is seldom likely to change the clinical course of a disease- but we insist that things like timing of rrt, controlling temperature, having a uniform MAP target, random drugs in sepsis like vit c and statins are going to change outcomes.

I believe the things we should be studying are how to make more accurate and rapid diagnoses, and how to better individualise therapy towards pts. Why does one LOL have a MAP of 50 for a day then walk out of the ICU 24 hrs later without any organ injury while another rapidly dies.
 
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LOVIT. Over 800 patients. Multicentre RCT. Seems well done. Vitamin C demonstrates clear harm. Good bye Vitamin C.

I've worked at tertiary centres where this was being used. Makes me feel a little sick.

I have to be honest and say I was a little bit excited after CITRIS-ALI. But I'm becoming ever more cynical and jaded and better understanding of my older colleagues who've seen it all before when it comes to new trials.

Also: Van den Berghe with the Leuven trials and tight glycemic control. Rivers and EGDT. Marick and his cocktail. You either die a hero or live long enough to become the villain.

Also: low tidal volumes, antibiotics, arguing about source control, and being meticulous about not doing anything stupid. Is that all we have to offer as a speciality? I'm only half joking. It's painful to see yet another negative trial.

Conclusion:
In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo.

Methods:
In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28.

Results:
A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P=0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event.

I just like the trial name because it’s exactly how I feel…

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I’m just waiting the probiotic or fecal transplant trial for critical illness induced MODS.

The Colo-Reductive Application of Probiotics… or the CRAP trial.

J/K… it’s already been done…

SCIENCE!
 
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Ivermectin for CoV, to answer your question.

Interestingly enough, both therapies pushed heavily by Paul Marik and both therapies ended up at best showing no benefit and at worst causing serious harm. Marik was a snake oil salesman through and through.
 
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Was Vitamin C ever alive?

Time clouds the picture, but I think I remember hearing about Marik’s (single center, very small) trial, then the immediate explosion in lay media about a “sepsis cure”, followed by an almost-as-immediate “waaaaaaait a minute….is this too good to be true?”. Then study after study after study after study showed no mortality benefit from the Vit C or the cocktail.
I'm not sure about lay media, but in the EM community this got pushed big time by some of the podcasts, like Emrap, Emcrit, etc. I distinctly remember Marik getting interviewed by Weingart claiming that septic patients no longer died at EVMS. It was prominent enough that our community hospital briefly considered putting something like this into place before we decided to defer until there was actually a trial of it.

Man, marik has such a mixed legacy. His stuff on lactate and CVP was really practice, or at least paradigm, changing. Although maybe he was just better at publicizing himself than others.

Sorry for the pedantry, however I would argue that ivermectin is a poor analogy--it was never accepted by mainstream practitioners. The true parallel is hydroxychloroquine. I'm old enough to remember when it was pushed by MGH, Duke, MD Anderson, et al...
 
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